Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510006, China.
Biomater Sci. 2020 Mar 31;8(7):1885-1896. doi: 10.1039/c9bm01927h.
In order to improve active tumor targeting, tumor cell uptake efficiency and circulation time of doxorubicin (DOX) in vivo, we constructed a cleavable PEGylated hyaluronic acid nano-drug delivery system (HA-mPEG2k-DOX) based on a tumor microenvironment pH-responsive imine bond. In this study, HA-mPEG2k-DOX can self-assemble into stable nanoparticles (HA-mPEG2k-DOX NPs) with a particle size of 50 nm. And the NPs can efficiently target CD44 positive CT26 cells and the pH-responsive cleavable PEG shell can be detached under weakly acidic environments and effectively promote the cellular uptake of HA-DOX NPs. Compared with DOX·HCl, the HA-mPEG2k-DOX NPs can significantly increase the DOX circulation time by 12.5 times, efficiently target the tumor tissues of CT26 tumor-bearing mice and remain for 72 hours. Therefore, the antitumor results in vivo indicated that the HA-mPEG2k-DOX NPs have the best anti-tumor effect while reducing the toxicity of the DOX. Overall, the cleavable PEGylated HA-mPEG2k-DOX NPs responding to pH-sensitive imine bonds, while actively targeting CD44-positive tumor cells, improve the dilemma of cellular uptake and delivery by the PEGylated nano delivery system.
为了提高阿霉素（DOX）在体内的主动肿瘤靶向、肿瘤细胞摄取效率和循环时间，我们构建了一种基于肿瘤微环境 pH 响应腙键的可裂解聚乙二醇化透明质酸纳米药物递送系统（HA-mPEG2k-DOX）。在本研究中，HA-mPEG2k-DOX 可以自组装成粒径为 50nm 的稳定纳米颗粒（HA-mPEG2k-DOX NPs）。并且 NPs 可以有效地靶向 CD44 阳性 CT26 细胞，在弱酸性环境下可分离出 pH 响应可裂解的聚乙二醇壳，并有效促进 HA-DOX NPs 的细胞摄取。与 DOX·HCl 相比，HA-mPEG2k-DOX NPs 可使 DOX 的循环时间延长 12.5 倍，显著提高 DOX 在 CT26 荷瘤小鼠肿瘤组织中的靶向效率，并保持 72 小时。因此，体内抗肿瘤结果表明，HA-mPEG2k-DOX NPs 在降低 DOX 毒性的同时，具有最佳的抗肿瘤效果。总的来说，对 pH 敏感腙键有响应的可裂解聚乙二醇化 HA-mPEG2k-DOX NPs，同时主动靶向 CD44 阳性肿瘤细胞，改善了 PEG 化纳米递药系统的细胞摄取和递送困境。
